Ultrasound Obstet Gynecol 2013; 41: 7–8 Published online in Wiley Online Library (wileyonlinelibrary.com).
Referee Commentaries
Re: Hematologic profile of neonates with growth restriction is associated with rate and degree of prenatal Doppler deterioration. A. A. Baschat, M. Kush, C. Berg, U. Gembruch, K. H. Nicolaides, C. R. Harman, O. M. Turan. Ultrasound Obstet Gynecol 2013; 41: 66–72. In this issue of the Journal, you will read a retrospective study of 103 fetuses that were small due to placental insufficiency. The aim of this study was to test the hypothesis that in fetuses with intrauterine growth restriction (IUGR) due to placental disease, the reduction in platelet count at birth is related to the rate of
Copyright 2013 ISUOG. Published by John Wiley & Sons, Ltd.
REFEREE COMMENTARIES
Referee Commentaries
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preceding cardiovascular deterioration. For this reason, the population was grouped into three: those delivering within 4, 6 and 9 weeks from diagnosis of placental insufficiency. The authors report that the strongest association of moderate and rapid deterioration was with a low platelet count. Placental consumption of platelets or dysfunctional erythropoiesis and thrombopoiesis are the most likely possible causes suggested by the authors. Over the last decade, there have been significant advances in our understanding of placental dysfunction and the fetal response. The current manuscript helps in furthering our knowledge of the pathophysiology of this condition. Hypoxia due to placental dysfunction is mainly responsible for fetal vasoconstriction in the placenta and the increased resistance in the vessels of IUGR fetuses1,2 . In the study of Baschat et al., FGR due to placental insufficiency was defined as abdominal circumference < 5th percentile and umbilical artery pulsatility index elevated to ≥ 2 SD above the gestational mean. This cannot be challenged. It is highly unlikely that some normally grown small fetuses were present in this cohort. Many measurement parameters (fetal Doppler, platelet count, fetal hemoglobin) are dependent on the gestational age. To remove this dependence, the authors converted all these into Z-scores (Z = (observed value – expected value)/SD). Z-scores tell us the extent of deviation of the observed measurement (the larger the deviation of Z from zero, the more unlikely the result is due to chance). The median enrollment-to-delivery intervals in the cases with slow and rapid deterioration were 39 (range, 10–86) days and 23 (range, 2–59) days, respectively. This suggests that groups for rapid, moderate and slow deterioration were somewhat arbitrary and there was at least some overlap, as evidenced from the ranges. Due to the design of the study, at least three measurements were required in each case, and the authors had to exclude those with fewer than three observations. It is quite possible that women with the most rapid rate of progression had to be excluded because delivery was required before three sets of observations could be obtained. The study does not tell us if low platelet count is a cause or the effect of placental dysfunction: it is possible that a rapid rate of hypoxia leads to endothelial dysfunction, platelet activation and consumption; it is equally possible that placental platelet consumption and progressive villous vascular occlusion results in accelerated cardiovascular deterioration. Although the findings are of limited clinical
Copyright 2013 ISUOG. Published by John Wiley & Sons, Ltd.
utility and do not change current management, they help us in the understanding of fetal response to placental dysfunction. It has been known for some time that nucleated red blood cell count is higher at birth in IUGR fetuses3 . This suggests that fetal hypoxia does not lead to significant myelosuppression. As the authors acknowledged, they had no information on the balance of hematopoietic regulatory factors such as erythropoietin or thrombpoietin. Studies which measure these levels would further help our understanding. The link between platelet activation and placental function explains the results of the systematic review and meta-analysis that found that low-dose acetylsalicylic acid started before 16 weeks is associated with a significant reduction of IUGR (relative risk, 0.51 (95% CI, 0.28–0.92)4 . However, hypoxia is not the only explanation for the increased fetoplacental resistance seen in fetuses with placental insufficiency. The placental size is smaller, the vessels narrower, the villi sparser, the fetal blood more viscous and the fetal cardiovascular function altered in pregnancies affected by growth restriction. Findings in cases of IUGR are likely to be related to a combination of several factors. A. Bhide Fetal Medicine Unit, St. George’s Hospital, London, SW17 0QT, UK (e-mail:
[email protected]) DOI: 10.1002/uog.12368
References 1. Sebire N, Talbert D. The dynamic placenta: a closer look at the pathophysiology of placental hemodynamics in uteroplacental compromise. Ultrasound Obstet Gynecol 2001; 18: 557–561. 2. Kingdom J, Burrell S, Kaufmann P. Pathology and clinical implications of abnormal umbilical artery Doppler waveforms. Ultrasound Obstet Gynecol 1997; 9: 271–286. 3. Minior VK, Shatzkin E, Divon MY. Nucleated red blood cell count in the differentiation of fetuses with pathologic growth restriction from healthy small-for-gestational-age fetuses. Am J Obstet Gynecol 2000; 182: 1107–1109. 4. Bujold E, Morency AM, Roberge S, Lacasse Y, Forest JC, Gigu`ere Y. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J Obstet Gynaecol Can 2009; 31: 818–826.
Ultrasound Obstet Gynecol 2013; 41: 7–8.
